The FANCA to FANCZ of DNA interstrand crosslink repair: Lessons from Fanconi anemia

Abstract

Interstrand crosslinks (ICLs) are produced by metabolic, environmental, and chemotherapeutic agents that chemically link the double helix of DNA. Many lessons about how ICLs are repaired have been learned by study of the ICL-sensitive disorder, Fanconi anemia (FA). The FA pathway consists of at least 19 FANC gene products that coordinate detection, excision, recombination, and replication bypass of this most complex of DNA lesions. Different steps in ICL repair are prone to mutagenic errors that promote cancer or cell death. Here we review the molecular details of the FA pathway, and the links between ICL repair in both cancer initiation and treatment.